myeloproliferative disorders Flashcards
What are the 4 main myeloproliferative disorders?
Chronic myelogenous leukemia (CML), Polycythemia vera, Myelofibrosis, Essential thrombocytosis
Describe main characteristics of polycythemia vera
Elevated red cell mass and Elevated hemoglobin and hematocrit
What are the 3 main causes of polycythemia in general?
Appropriately elevated erythropoietin: hypoxemia. Inappropriately elevated erythropoietin: renal cell carcinoma, hepatocellular carcinoma. Germline and somatic mutation: polycythemia vera
What are some epidemiological points of polycythemia vera?
Average age at diagnosis is 60 years of age. Men more common then women.Survival if untreated is 6-18 months. If treated the survival is > 10 years
What are symptoms associated with polycythemia vera?
pruritis post bathing, erythromelaglia, HA, weakness, dizziness, excessive sweating
What symptoms related to thrombosis are seen with polycythemia vera?
Arterial and venous thrombosis. Amaurosis fugax, Scintillating scotomata (opthlamic migraine, decreased retinal and choroidal blood flow due to increased blood viscosity)
What lab abnormalities are seen with polycythemia vera?
Hgb/HCT > 18.5/56 or > 16.5/50 women. WBC > 10.5. Platlets > 450 K. Elevated serum lactate dehydrogenase. JAK2 mutation in 98%. Abnormal serum erythropoietin. Hypercellular bone marrow. Iron storage in bone marrow is absent
What physical findings are expected with polycythemia vera?
Splenomegaly, Facial plethora (ruddy cyanosis), Hepatomegaly, Injection of conjunctival small vessels &/or engorged veins of the optic fundus, Excoriation of the skin, Gouty arthritis and tophi
What is treatment for polycythemia vera?
Phlebotomy to keep HCT < 45 men; < 42 women. Low dose aspirin 75-100 mg. Myelosuppressive agents: Hydroxyurea (add if the above treatments are not working or if at high risk for thrombosis with age > 60 or prior thrombotic episode) OR Interferon alpha (use instead of hydroxyurea in women of childbearing age or if hydroxyurea is ineffective)
What more serious disorders can polycythemia progress to?
myelofibrosis or acute leukemia
What is myelofibrosis?
Replacement of the marrow with collagenous connective tissue fibers
What is the epidemiology of myelofibrosis?
Least frequent of the chronic myeloproliferative disorders. Median age 67. Occurs more often in men then women
What are major causes of morbidity and mortality associated with myelofibrosis?
Progression to acute leukemia. Infection. Bleeding. Portal hypertension. Vascular complications
What clinical manifestations are associated with myelofibrosis?
severe fatigue, LUQ pain(splenomegaly), weight loss, low fever, night sweats, hepatomegaly
What symptoms could be secondary to hepatomegaly in myelofibrosis?
Portal hypertension, Ascites, Esophageal and gastric varices, GI bleeding, Hepatic encephalopathy, Portal vein thrombosis
What does a blood smear of myelofibrosis show?
Marked poikilocytosis (variation in cell shape) with the presence of tear-drop poikilocytes. There is also anisocytosis.
What does a bone marrow biopsy typically show for myelofibrosis?
at early stage: high white count with a left shift, and a hypercellular marrow. at late stage: marrow is replaced with fibrous tissue
What are treatment options for myelofibrosis?
Stem cell transplant. Hydroxyurea. chemotherapeutic agents. JAK2 inhibitors: ruxolitinib (Jakafi) $9K/month. Splenectomy but may cause worsening hepatomegaly and decline in liver function. Radiation therapy
What is essential thrombocytosis?
Uncommon myeloproliferative condition in which there is isolated thrombocytosis. Abnormal platelet function that can lead to thrombosis and bleeding. Occurs age > 50, more common in women
What are lab results associated with essential thrombocytosis?
Platelet counts can be markedly elevated. White blood counts may be slightly elevated. normal RBC morphology. Bone marrow biopsy reveals increased numbers of megakaryocytes. High frequency of JAK2 mutations
What are symptoms secondary to elevated platelet count in essential thrombocytosis?
HA, Lightheadedness, Visual changes, Numbness, tingling or burning in the feet (erythromelalgia, Splenomegaly, History of thrombosis
Where is thrombosis likely to occur?
Arterial thrombosis is most likely to occur in the hands, feet and brain. Venous thrombosis of mesenteric, hepatic and portal vein, and deep vein thrombosis
What are treatment options for essential thrombocytosis?
Low dose aspirin (81 mg/day) and Hydroxyurea to keep platelet count below 500,000
What can result as potential progression of essential thrombocytosis?
Bone marrow may become fibrotic. Massive splenomegaly may occur. progression to myelofibrosis after 15 years. progression to acute myelogenous leukemia over 20 years
